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Novel Complement C5 Small-interfering RNA Lipid Nanoparticle Prolongs Graft Survival in a Hypersensitized Rat Kidney Transplant Model
Conclusions. C5 siRNA-LNP combined with immunosuppressants CsA and DSG downregulated C5 activity and significantly prolonged graft survival compared with control siRNA-LNP with CsA and DSG. Downregulation of C5 expression using C5 siRNA-LNP may be an effective therapeutic approach for AMR.
Source: Transplantation - December 1, 2022 Category: Transplant Surgery Tags: Original Basic Science Source Type: research

Engineered Extracellular Vesicles From Human Periodontal-Ligament Stem Cells Increase VEGF/VEGFR2 Expression During Bone Regeneration
Conclusion In conclusion our results evidenced that 3D-COL/hPDLSCs/PEI-EVs may be an efficacious strategy to induce bone regeneration and vascularization of bone defects, thanks to its capacity to increase the levels of VEGF. Ethics Statement The study was performed in accordance with the guidelines of the Helsinki Declaration (2013). The written approval for the human periodontal ligament collection performed in this study has been obtained from the Medical Ethics Committee at the Medical School, “G. d’Annunzio” University of Chieti–Pescara, Chieti, Italy (n°266/17.04.14, Principal in...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

Ocular Instillation of Vitamin A-Coupled Liposomes Containing HSP47 siRNA Ameliorates Dry Eye Syndrome in Chronic Graft-Versus-Host Disease
Chronic graft-versus-host disease (GVHD) is characterized by multiorgan fibrosis and affects the quality of life of transplant survivors. Ocular manifestations are found in 40-60% of GVHD patients, and the most common symptom is dry eye syndrome associated with lacrimal gland fibrosis. We previously demonstrated heat shock protein 47 (HSP47), a collagen specific molecular chaperone, plays a critical role in excessive collagen synthesis in chronic GVHD, and systemic administration of vitamin A-coupled liposomes carrying HSP47 siRNA (VA-lip HSP47) ameliorates skin and salivary gland fibrosis in chronic GVHD (Yamakawa, et al, Blood 2018).
Source: Biology of Blood and Marrow Transplantation - January 31, 2019 Category: Hematology Authors: Hiroyuki Ohigashi, Daigo Hashimoto, Shuichiro Takahashi, Tomohiro Yamakawa, Eiko Hayase, Takanori Teshima Tags: 229 Source Type: research

Vitamin A-coupled liposomes containing siRNA against HSP47 ameliorate skin fibrosis in chronic graft-versus-host disease
Chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (SCT) is characterized by multiorgan fibrosis and profoundly affects the quality of life of transplant survivors. Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, plays a critical role in collagen synthesis in myofibroblasts. We explored the role of HSP47 in the fibrotic process of cutaneous chronic GVHD in mice. Immunohistochemical analysis showed massive fibrosis with elevated amounts of collagen deposits and accumulation of F4/80+ macrophages, as well as myofibroblasts expressing HSP47 and retinol-bin...
Source: Blood - March 29, 2018 Category: Hematology Authors: Yamakawa, T., Ohigashi, H., Hashimoto, D., Hayase, E., Takahashi, S., Miyazaki, M., Minomi, K., Onozawa, M., Niitsu, Y., Teshima, T. Tags: Transplantation Source Type: research

Concurrent CCR7 Overexpression and RelB Knockdown in Immature Dendritic Cells Induces Immune Tolerance and Improves Skin-Graft Survival in a Murine Model
Conclusion: Transfection with Ad-CCR7 and RelB KD in imDCs may be an effective approach inducing immune tolerance, thus being potentially valuable for inhibiting allograft rejection.Cell Physiol Biochem 2017;42:455 –468
Source: Cellular Physiology and Biochemistry - June 2, 2017 Category: Cytology Source Type: research

Upregulation of PIM2 by Underexpression of MicroRNA-135-5p Improves Survival Rates of Skin Allografts by Suppressing Apoptosis of Fibroblast Cells.
CONCLUSIONS MiR-135-5p is involved with the prognosis of burn patients after skin transplantation. PIM2 is a virtual target of miR-135-5p, and there is a negative regulatory relationship between miR-135-5p and PIM2. MiR-135-5p and PIM2 interfered with the viability and apoptosis in cells. PMID: 28064305 [PubMed - in process]
Source: Medical Science Monitor - January 13, 2017 Category: Research Tags: Med Sci Monit Source Type: research

Programmed cell death 1 (PD-1) regulates the effector function of CD8 T cells via PD-L1 expressed on target keratinocytes.
Abstract Programmed cell death 1 (PD-1) is an inhibitory molecule expressed by activated T cells. Its ligands (PD-L1 and -L2; PD-Ls) are expressed not only by a variety of leukocytes but also by stromal cells. To assess the role of PD-1 in CD8 T cell-mediated diseases, we used PD-1-knockout (KO) OVA-specific T cell-receptor transgenic (Tg) CD8 T cells (OT-I cells) in a murine model of mucocutaneous graft-versus-host disease (GVHD). We found that mice expressing OVA on epidermal keratinocytes (K14-mOVA mice) developed markedly enhanced GVHD-like disease after transfer of PD-1-KO OT-I cells as compared to those mice...
Source: Journal of Autoimmunity - July 18, 2014 Category: Allergy & Immunology Authors: Okiyama N, Katz SI Tags: J Autoimmun Source Type: research

Novel nanosome delivery system combined with siRNA targeting the antimicrobial gene DFB4: A new approach for psoriasis management?
This study encourages the exploration of topical gene silencing strategies in dermatology, and refocuses our attention on both, the role of hBD2 in psoriasis pathogenesis, and the thorny question which animal model reflects human psoriasis most faithfully. This article is protected by copyright. All rights reserved.
Source: Experimental Dermatology - March 28, 2014 Category: Dermatology Authors: A Keren, M David, A Gilhar Tags: Commentary from the Editorial Board Source Type: research

RNAi functionalized collagen-chitosan/silicone membrane bilayer dermal equivalent for full-thickness skin regeneration with inhibited scarring.
Abstract Scar inhibition of dermal equivalent is one of the key issues for treatment of full thickness skin defects. To yield a bioactive RNAi functionalized matrix for skin regeneration with inhibited scarring, collagen-chitosan/silicone membrane bilayer dermal equivalent (BDE) was combined with trimetylchitosan (TMC)/siRNA complexes which could induce suppression of transforming growth factor-β1 (TGF-β1) pathway. The RNAi-BDE functioned as a reservoir for the incorporated TMC/siRNA complexes, enabling a prolonged siRNA release. The seeded fibroblasts in the RNAi-BDE showed good viability, internalized the TMC/...
Source: Biomaterials - January 4, 2013 Category: Materials Science Authors: Liu X, Ma L, Liang J, Zhang B, Teng J, Gao C Tags: Biomaterials Source Type: research